crossing96/oncoscreening huggingface dataset:
Urinary metabolomics for discovering metabolic biomarkers of bladder cancer by UPLC-MS.	Bladder cancer (BC) is one of the most frequent cancer in the world, and its incidence is rising worldwide, especially in developed countries. Urine metabolomics is a powerful approach to discover potential biomarkers for cancer diagnosis. In this study, we applied an ultra-performance liquid chromatography coupled to mass spectrometry (UPLC-MS) method to profile the metabolites in urine from 29 bladder cancer patients and 15 healthy controls. The differential metabolites were extracted and analyzed by univariate and multivariate analysis methods. Together, 19 metabolites were discovered as differently expressed biomarkers in the two groups, which mainly related to the pathways of phenylacetate metabolism, propanoate metabolism, fatty acid metabolism, pyruvate metabolism, arginine and proline metabolism, glycine and serine metabolism, and bile acid biosynthesis. In addition, a subset of 11 metabolites of those 19 ones were further filtered as potential biomarkers for BC diagnosis by using logistic regression model. The results revealed that the area under the curve (AUC) value, sensitivity and specificity of receiving operator characteristic (ROC) curve were 0.983, 95.3% and 100%, respectively, indicating an excellent discrimination power for BC patients from healthy controls. It was the first time to reveal the potential diagnostic markers of BC by metabolomics, and this will provide a new sight for exploring the biomarkers of the other disease in the future work.	bladder
Impact of the Use of Proton Pump Inhibitors on Pembrolizumab Effectiveness for Advanced Urothelial Carcinoma.	BACKGROUND/AIM: This study aimed to clarify the impact of proton pump inhibitors (PPIs) on oncological outcomes in patients who received pembrolizumab for advanced urothelial carcinoma (UC). PATIENTS AND METHODS: Forty advanced UC patients treated with pembrolizumab were retrospectively reviewed and divided into two groups (PPI: 15 patients; without PPI: 25 patients). Tumor response and survival were compared between these groups. The factors associated with survival were also investigated. RESULTS: The objective response rate was significantly lower in the group with PPIs compared with the group without PPIs. Both progression-free survival (PFS) and overall survival (OS) were significantly shorter in the group with PPIs than in the group without PPIs. The use of PPIs was a significant predictor of poor PFS and OS in multivariate analysis. CONCLUSION: The use of PPIs was negatively associated with tumor response and survival in patients with advanced UC treated with pembrolizumab.	bladder
Multi-country clinical practice patterns, including use of biomarkers, among physicians' treatment of BCG-unresponsive non-muscle invasive bladder cancer (NMIBC).	BACKGROUND: Intravesical bacillus Calmette-Guérin (BCG) fails in a considerable proportion of non-muscle invasive bladder cancer (NMIBC) patients despite treatment per recommended protocol. This real-world study aimed to understand the current patterns of treatment and disease management for the broad BCG-unresponsive NMIBC patient population, alongside collecting sufficient data on patients who do not undergo cystectomy. METHODS: This was a multicenter, retrospective survey of physicians treating BCG-unresponsive NMIBC patients. Data were collected in eight countries - France, Germany, Spain, Italy, United Kingdom, United States, China, and Japan - between January and May 2019. The study consisted of a short online physician survey and a retrospective chart review of eligible BCG-unresponsive NMIBC patients. Physicians abstracted chart data for the last 10 (five patients in Japan) eligible BCG-unresponsive NMIBC patients meeting the inclusion criteria, and the data were analysed for all countries combined using descriptive statistics. Country-specific analyses were also carried out, as appropriate. RESULTS: Overall, 508 physicians participated in the study. Almost one-quarter (22.9%) of physicians' current NMIBC patient caseload was BCG-unresponsive, whereby BCG therapy was no longer considered an option. Half of physicians (49.4%) did not regularly use biomarker tests in their practice, with particularly few physicians undertaking biomarker testing in Spain and Japan. Biomarker testing varied considerably, with the proportions of physicians selecting 'none' ranging from 11.4% in China to 70.3% in Japan. Physicians reported transurethral resection of the bladder tumor (TURBT) and BCG as the most common current treatments received by their patients. Chemotherapy and anti-PD-L1 treatment options were considered impactful new therapies by 94.7% and 90.0% of physicians surveyed in this study, respectively. CONCLUSIONS: The most common treatments received by patients in this study were TURBT and BCG. Emerging new treatments are driven by exploring biomarkers, but in real-world clinical practice only half of physicians or fewer regularly tested their NMIBC patients for biomarkers; PD-1/PD-L1 was the most common biomarker test used. Most physicians reported that, in addition to chemotherapy, anti-PD-L1 was an impactful new therapy.	bladder
Immediate radical cystectomy versus BCG immunotherapy for T1 high-grade non-muscle-invasive squamous bladder cancer: an international multi-centre collaboration.	PURPOSE: To compare cancer-specific mortality (CSM) and overall mortality (OM) between immediate radical cystectomy (RC) and Bacillus Calmette-Guérin (BCG) immunotherapy for T1 squamous bladder cancer (BCa). METHODS: We retrospectively analysed 188 T1 high-grade squamous BCa patients treated between 1998 and 2019 at fifteen tertiary referral centres. Median follow-up time was 36 months (interquartile range: 19-76). The cumulative incidence and Kaplan-Meier curves were applied for CSM and OM, respectively, and compared with the Pepe-Mori and log-rank tests. Multivariable Cox models, adjusted for pathological findings at initial transurethral resection of bladder (TURB) specimen, were adopted to predict tumour recurrence and tumour progression after BCG immunotherapy. RESULTS: Immediate RC and conservative management were performed in 20% and 80% of patients, respectively. 5-year CSM and OM did not significantly differ between the two therapeutic strategies (Pepe-Mori test p = 0.052 and log-rank test p = 0.2, respectively). At multivariable Cox analyses, pure squamous cell carcinoma (SqCC) was an independent predictor of tumour progression (p = 0.04), while concomitant lympho-vascular invasion (LVI) was an independent predictor of both tumour recurrence and progression (p = 0.04) after BCG. Patients with neither pure SqCC nor LVI showed a significant benefit in 3-year recurrence-free survival and progression-free survival compared to individuals with pure SqCC or LVI (60% vs. 44%, p = 0.04 and 80% vs. 68%, p = 0.004, respectively). CONCLUSION: BCG could represent an effective treatment for T1 squamous BCa patients with neither pure SqCC nor LVI, while immediate RC should be preferred among T1 squamous BCa patients with pure SqCC or LVI at initial TURB specimen.	bladder
An immune-related lncRNA model for predicting prognosis, immune landscape and chemotherapeutic response in bladder cancer.	Long noncoding RNAs (lncRNAs) participate in cancer immunity. We characterized the clinical significance of an immune-related lncRNA model and evaluated its association with immune infiltrations and chemosensitivity in bladder cancer. Transcriptome data of bladder cancer specimens were employed from The Cancer Genome Atlas. Dysregulated immune-related lncRNAs were screened via Pearson correlation and differential expression analyses, followed by recognition of lncRNA pairs. Then, a LASSO regression model was constructed, and receiver operator characteristic curves of one-, three- and five-year survival were established. Akaike information criterion (AIC) value of one-year survival was determined as the cutoff of high- and low-risk subgroups. The differences in survival, clinical features, immune cell infiltrations and chemosensitivity were compared between subgroups. Totally, 90 immune-related lncRNA pairs were identified, 15 of which were screened for constructing the prognostic model. The area under the curves of one-, three- and five-year survival were 0.806, 0.825 and 0.828, confirming the favorable predictive performance of this model. According to the AIC value, we clustered patients into high- and low-risk subgroups. High-risk score indicated unfavorable outcomes. The risk model was related to survival status, age, stage and TNM. Compared with conventional clinicopathological characteristics, the risk model displayed higher predictive efficacy and served as an independent predictor. Also, it could well characterize immune cell infiltration landscape and predict immune checkpoint expression and sensitivity to cisplatin and methotrexate. Collectively, the model conducted by paring immune-related lncRNAs regardless of expressions exhibits a favorable efficacy in predicting prognosis, immune landscape and chemotherapeutic response in bladder cancer.	bladder
Immunohistochemical Screening of Upper Tract Urothelial Carcinomas for Lynch Syndrome Diagnostics: A Systematic Review.	OBJECTIVE: To review the effect of universal screening of newly diagnosed upper tract urothelial carcinomas (UTUC) for mismatch repair (MMR) protein loss to aid in Lynch syndrome diagnostics. MATERIALS AND METHODS: Studies were identified through PubMed on December 1, 2021. Eligibility criteria were universal immunohistochemical analyses for at least 2 MMR proteins in unselected, consecutively collected UTUC cohorts. Exclusion criteria included reviews, case-reports, non-English language, and non-humans. Risk of bias was assessed using a modified Newcastle-Ottawa scale. Meta-analyses were performed to compare the association between clinical criteria and Lynch syndrome diagnoses. RESULTS: From 12 included studies, 1628 surgically removed UTUC from 1626 patients were screened for MMR protein loss. In 11 studies, 140 of the 1559 patients had tumors with loss (9.0%) with 80.7% showing loss of MSH2, MSH6, or both. In 7 studies, genetic testing confirmed Lynch syndrome diagnosis for 20 of 970 patients (2.1%). In 8 studies, 31 patients were given a clinical Lynch syndrome diagnosis (2.6%). In total, 51 assumed or verified Lynch syndrome patients were identified among 1087 patients (4.7%). Meta-analyses of 3 studies showed significant association between previous cancer diagnosis and Lynch syndrome-associated UTUC (P = .038). CONCLUSION: Despite the few studies conducted and lack of genetic testing, current data suggests that universal screening for MMR protein loss in UTUC may result in Lynch syndrome diagnoses in 4.7%. However, for the screening to be effective for Lynch syndrome diagnostics, follow-up investigations, such as genetic testing for MMR variants, are needed.	bladder
Outcomes by time to definitive chemoradiation treatment for patients with muscle-invasive bladder cancer.	BACKGROUND: The coronavirus disease 2019 (COVID-19) pandemic has raised concerns about delaying treatment for localized cancer and its impact on long-term outcomes. OBJECTIVE: We aimed to investigate the impact of time to chemoradiation (CRT) on recurrence and survival outcomes for patients with muscle-invasive bladder cancer (MIBC). METHODS: In the national Veterans Affairs' database, we identified patients with urothelial histology, MIBC (T2-4a/N0-3/M0) diagnosed between 2000 to 2018 and treated with definitive CRT. Time to treatment was defined as the number of days between date of diagnosis and start date of CRT. The cohort was stratified into < 90 (early) or ≥ 90 days (delayed) groups. Endpoints of locoregional failure (LRF), distant failure (DF), overall survival (OS), and bladder cancer-specific survival (BCS) were evaluated in multivariable Cox and Fine-Gray models. RESULTS: 305 patients with MIBC underwent CRT - 190 (62.3%) received early CRT, 115 (37.7%) received delayed CRT. Multivariable analysis (including success of transurethral resection of bladder tumor and type of chemotherapy) revealed no difference in recurrence between groups - LRF HR 1.12 (95%CI 0.76-1.67, P = 0.56) and DF HR 1.03 (95%CI 0.70-1.53, P = 0.88). Similarly, there were no differences in survival outcomes. The lack of association was maintained at both earlier and later time cutoffs (60-120 days). CONCLUSIONS: Our findings suggest that a short-term delay in definitive therapy may not affect long-term outcomes for patients with MIBC undergoing CRT. This study does not endorse delays in therapy, but rather provides information to aid patients and clinicians navigate the unique challenges of MIBC care in both pandemic and non-pandemic times.	bladder
DNA Hypomethylation Is Associated with the Overexpression of INHBA in Upper Tract Urothelial Carcinoma.	Urothelial carcinoma includes upper urinary tract cancer (UTUC) and bladder cancer. Although nephroureterectomy is the standard treatment for UTUC, the recurrence rate is approximately half and the tumor is associated with poor prognoses. Metastases are the most devastating and lethal clinical situation in urothelial carcinoma. Despite its clinical importance, few potential diagnostic biomarkers are suitable for early UC detection. We compared high-stage/high-grade urothelial carcinoma tissues to adjacent normal urothelial tissues using methyl-CpG binding domain protein capture for genome-wide DNA methylation analysis. Based on our findings, inhibin βA (INHBA) might be associated with carcinogenesis and metastasis. Further, clinical UC specimens had significant INHBA hypomethylation based on pyrosequencing. INHBA was detected by real-time PCR and immunohistochemistry staining, and was found to be highly expressed in clinical tissues and cell lines of urothelial carcinoma. Further, INHBA depletion was found to significantly reduce BFTC-909 cell growth and migration by INHBA-specific small interfering RNA. Interestingly, a positive correlation was found between SMAD binding and extracellular structure organization with INHBA using gene set enrichment analysis and gene ontology analysis. Together, these results are the first evidence of INHBA promoter hypomethylation and INHBA overexpression in UTUC. INHBA may affect urothelial carcinoma migration by reorganizing the extracellular matrix through the SMAD pathway.	bladder
Management of Upper Tract Urothelial Carcinoma.	PURPOSE OF REVIEW: We review the epidemiology, risk factors, diagnosis, and treatment of upper tract urothelial carcinoma (UTUC), with a distinction between the different risk groups. RECENT FINDINGS: Endoscopic treatment with laser ablation of tumors has an evolving role in treating low-grade UTUC including select large and multifocal tumors, along with complementary topical chemotherapeutic treatment that can reach difficult intrarenal locations. Template lymphadenectomy is recommended in patients undergoing nephroureterectomy. A recent randomized control trial showed benefit of adjuvant chemotherapy after radical nephroureterectomy for locally advanced disease. Advances in immunologic therapy have shown promise in treating metastatic UTUC, and immunologic-based therapies have been incorporated into treatment regimens. Notable progress has been made in both the surgical and medical treatment arms for UTUC, thus extending the reach of nephron-sparing therapy for those with localized disease and increasing overall survival for those with locally advanced disease.	bladder
Evolution of immunotherapy in the treatment of non-muscle-invasive bladder cancer.	INTRODUCTION: Immunotherapy with intravesical bacillus Calmette-Guérin (BCG) has been the gold standard treatment for intermediate- and high-risk non-muscle-invasive bladder cancer (NMIBC) for nearly half a century. Yet, many patients with high-risk disease will experience recurrence, including those who progress and eventually become unresponsive to BCG. For decades, apart from radical cystectomy, few therapeutic options existed for this at-risk population. However, the advent of novel immunotherapeutic agents has transformed treatment in a range of tumor types, including urothelial carcinoma. These immunotherapies have yielded promising results in the treatment of metastatic urothelial carcinoma and, as such, are also being investigated for use in NIMIBC. AREAS COVERED: This article provides an overview of the evolution of immunotherapy for NMIBC, beginning from the original immunotherapy-BCG - to current agents including checkpoint inhibitors, IL-15 agonists, viral gene therapies and therapeutic cancer vaccines. EXPERT OPINION: Emerging insights over the last decade have led to the development of novel immunotherapiesfor the treatment of NMIBC whilst providing new opportunities to enhance the anti-tumour activity of BCG. In particular, the KEYNOTE-057 trial represents a pivotal moment for immunotherapy in NMIBC, leading to approval of pembrolizumab by the US Food & Drug Administration for patients with BCG-unresponsive disease. However, patient selection and the development of biomarkers to guide the identification of patients who will benefit most from a particular immunotherapy remains critical. As research efforts come to fruition, these novel immunotherapies may become integrated into the standard treatment paradigm for intermediate- and high-risk NMBIC.	bladder
Predictive role of ferroptosis-related long non-coding RNAs in bladder cancer and their association with immune microenvironment and immunotherapy response.	BACKGROUND: We have previously reported that ferroptosis has an important role in bladder cancer development. In this study, we aimed to further explore the possible predictive ability of ferroptosis-related long non-coding RNAs (lncRNAs) in bladder cancer and their relation with immune microenvironment and immunotherapy response. MATERIALS AND METHODS: The ferroptosis-related lncRNAs were identified by Pearson's correlation analysis. The predictive lncRNA signature was developed by univariate and multivariate regression analyses. Only the main effects of independent variables in multivariate analysis were included in this signature. The TCGA dataset was defined as the training cohort and GEO was the validation cohort in this study. All samples were grouped into a high- or low-risk group depending on risk signature. The prognostic role of lncRNA signature was explored through survival analysis and receiver operating characteristic curve (ROC) analysis in both TCGA and GEO cohorts. Additionally, the independent prognostic ability of the lncRNA signature was confirmed by multivariate independent analysis. Furthermore, the relationship between lncRNAs and immune microenvironment as well as immunotherapy response in bladder cancers was studied. RESULTS: The Kaplan-Meier curves identified significantly poorer overall survival outcomes for high-risk groups in both TCGA (p < 0.001) and GEO (p < 0.001) cohorts. The area under the curve (AUC) during ROC analysis of 1, 3, and 5 years was 0.781 ± 0.046, 0.784 ± 0.027, and 0.817 ± 0.025, respectively, in the TCGA cohort and 0.665 ± 0.177, 0.719 ± 0.068, and 0.791 ± 0.055, respectively, in the GEO cohort. The multivariate independent analysis in TCGA cohort identified age (p = 0.003), stage (p < 0.001), and signature risk score (p < 0.001) as independent risk factors for overall survival. Furthermore, this study demonstrated a significant difference in infiltration levels of various immune cells between high- and low-risk groups. The high risk group tended to have a lower expression of proteins including PD1 (p < 0.01), PD-L1 (p < 0.01), CTLA-4 (p < 0.05), etc. corresponding to various immune checkpoints. Additionally, the immunotherapy trial confirmed that the high-risk group tended to have a poorer treatment response than the low-risk group (p < 0.001). CONCLUSIONS: The ferroptosis-related lncRNAs exhibited a good predictive capacity for overall survival in bladder cancer. Additionally, they could be utilized to reveal tumour-immune microenvironment and immunotherapy responses.	bladder
Clinical Outcomes and Prognosis Analysis of Younger Bladder Cancer Patients.	BACKGROUND: Generally, little is known about prognostic factors in bladder cancer patients under 40 years of age. We therefore performed a retrospective study to identify prognostic factors in these younger bladder cancer patients. METHODS: We collected clinicopathological data on bladder cancer patients ≤40 years old diagnosed between 1975 and 2018 from the Surveillance, Epidemiology, and End Results (SEER) database. Survival curves were generated using the Kaplan-Meier method, and the differences between groups were analyzed using the log-rank test. Univariate and multivariate Cox hazards regression analyses were performed to define hazard ratios (HRs) for cancer-specific survival (CSS). RESULTS: There were statistical differences in race, histological type, cancer stage, tumor size, and surgery treatment groups between overall survival and CSS. Only tumor size and cancer stage were significant independent prognostic risk factors in younger bladder cancer patients for the prediction of CSS. CONCLUSION: Tumors greater than 30 mm in size and a more advanced stage of bladder cancer were indicative of a poor prognosis in bladder cancer patients ≤40 years old, and long-term follow-up is suggested.	bladder
Circular RNA circSHPRH inhibits the malignant behaviors of bladder cancer by regulating the miR-942/BARX2 pathway.	Bladder cancer (BCa) is one of the most common tumors of the genitourinary system. However, the detailed molecular mechanism of BCa progression is still unclear. Recently, an increasing number of studies have demonstrated that circular RNAs (circRNAs) play a critical role in the tumorigenesis and progression of BCa. In this article, we showed that circSHPRH expression was obviously decreased in BCa tissues, compared with adjacent normal tissues. Moreover, a low circSHPRH level was positively correlated with a high grade, a high pathological stage, lymphatic metastasis and an unfavorable prognosis for BCa patients. Cell function studies indicated that silencing circSHPRH dramatically increased the proliferation, migration and invasion of BCa cells. Animal experiments revealed that circSHPRH overexpression repressed tumor growth. Mechanistic studies demonstrated that circSHPRH could combine with miR-942 and serve as a sponge of miR-942, which targets BARX2 in BCa cells. Rescue experiments showed that suppression of miR-942 or BARX2 overexpression could significantly abrogate the promoting effects of circSHPRH silencing on BCa cell proliferation and invasion. Furthermore, circSHPRH overexpression partly eliminated the suppressive effects of miR-942 on BARX2 expression. In addition, circSHPRH knockdown promoted activation of the Wnt/β-catenin signaling pathway by regulating BARX2. Taken together, our findings indicate that circSHPRH serves as a sponge of miR-942 to inhibit BCa progression by upregulating BARX2 expression, thereby inhibiting the Wnt/β-catenin signaling pathway.	bladder